The broad, long-term objectives are to contribute to the understanding of interactions of extremely low frequency (ELF) magnetic fields with living systems. The questions addressed are whether and through what mechanisms these fields may modify cancer development. The mouse skin model of multistage carcinogenesis is proposed to be used for this investigation, as this model is suitable for study of relatively subtle effects and mechanisms occurring though various cellular and molecular pathways. Preliminary results have suggested a co-promoting action of 60 Hz magnetic fields. The proposed investigations comprise two parallel, but closely integrated streams: (1) animal experiments with accompanying bioassays, such as ornithine decarboxylase activity, DNA synthesis, tumor suppressor gene regulation, an in vitro co-culture separate experiments and (2) electromagnetic dosimetry to evaluate induced electric fields and currents in various parts of the whole animal and on cellular and subcellular level, specifically for the target organ (skin). The main hypothesis tested in in-vitro co-culture experiments will be whether the induced electric field in tissue or the magnetic field or another parameter (e.g. the rate of change of magnetic field, DC magnetic field) are the critical parameters of the interaction. In the animal experiment groups (48 mice each) of juvenile female SENCAR mice, whose skins are once treated with a known cancer initiator (DMBA) and also weekly treated with various subthreshold doses of a chemical cancer promoter (TPA) will be exposed to a uniform (+/-10%) , 60 Hz magnetic fields at 2 mT and a lower strength either continuously or intermittently. It is estimated that doubling of the number of animals with tumors will be detected with a confidence level of 90%. A battery of bioassays will be aimed at identifying the biological interaction mechanism and cellular structures involved. Evaluations (through calculations and measurements) of electric fields and currents in anatomically correct models of mice and morphologically correct models of skin provide means for interspecies dose scaling and development of physical and biophysical interaction mechanisms. One of the aspects of interaction that will be scrutinized is inter-cellular communication.